IAG933 for Mesothelioma

Recruiting at 24 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Novartis Pharmaceuticals

Must not be taking: TEAD inhibitors

Disqualifiers: Other malignancies, Cardiac disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called IAG933 in patients with specific types of tumors. It aims to find the safest and most effective dose and see if the drug can help shrink the tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific timeframes for stopping certain cancer treatments before starting the trial, such as a 4-week period for some therapies. It's best to discuss your current medications with the trial team.

What makes the drug IAG933 unique for treating mesothelioma?

The drug IAG933 is unique for treating mesothelioma because it represents a novel approach compared to traditional chemotherapy, potentially involving a different mechanism of action or administration method, although specific details about its uniqueness are not provided in the available research. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for adults with advanced mesothelioma or solid tumors that have specific genetic mutations (NF2, LATS1/LATS2) or YAP/TAZ fusions. Participants must have tried all standard treatments without success, be unable to tolerate them, or no standard treatment exists. They should also be able to undergo a tumor biopsy and not have other serious health issues like poor bone marrow, kidney, liver function, significant heart disease risks, active COVID-19 infection or a history of certain lung diseases.

Inclusion Criteria

I have advanced mesothelioma and standard treatments haven't worked or aren't suitable for me.

I have an advanced solid tumor with an NF2 mutation and can't use standard treatments.

I have an advanced cancer that cannot be surgically removed.

Exclusion Criteria

My bone marrow is not working well.

I have had a serious lung condition from medication or other causes.

My kidneys are not working well.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Characterize the safety and tolerability of IAG933 and determine the maximum tolerated dose or recommended dose

1 year

Dose Expansion

Assess the preliminary anti-tumor activity and further assess the safety and tolerability at the recommended dose/maximum tolerated dose

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• IAG933 (CAR T-cell Therapy)

Trial Overview The study tests IAG933's safety and tolerability in patients with advanced mesothelioma and other solid tumors. It aims to find the highest dose patients can take without severe side effects (maximum tolerated dose) and suggest an optimal dose for further studies.

Participant Groups

Group I: Group 4 Experimental Treatment 1 Intervention

Non-pleural mesothelioma

Group II: Group 3 Experimental Treatment 1 Intervention

Solid tumors with functional YAP/TAZ fusions

Group III: Group 2 Experimental Treatment 1 Intervention

NF2 truncating mutations or deletions

Group IV: Group 1 Experimental Treatment 1 Intervention

Malignant pleural mesothelioma

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In a pilot study involving 19 patients with early-stage malignant pleural mesothelioma, the combination of intrapleural autologous activated macrophages (AM Phi) and gamma-interferon was well tolerated, with no major adverse effects reported during treatment.

The overall response rate to this therapy was limited, with only 14% of treated patients showing a response, although one patient remained disease-free for 69 months, indicating some potential for long-term benefit despite the low overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrapleural infusion of activated macrophages and gamma-interferon in malignant pleural mesothelioma: a phase II study. Monnet, I., Breau, JL., Moro, D., et al.[2019]

Malignant pleural mesothelioma (MPM) is a rare but increasing cancer linked to asbestos exposure, with a significantly higher incidence in occupationally exposed populations (100 cases/million/year) compared to the general population (1 case/million/year).

First-line treatment for MPM involves a combination of pemetrexed and cisplatin, which has been shown to improve overall survival and quality of life in phase 3 trials, while ongoing studies are exploring the potential of antiangiogenic agents like bevacizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update]. Porret, E., Madelaine, J., Galateau-Sallé, F., et al.[2008]

HEG1 is a highly effective marker for identifying malignant mesothelioma (MM) in effusion cytology, showing positive results in all tested cases of MM, while being negative in most carcinomas.

The study found that loss of BAP1 and MTAP, along with homozygous deletion of CDKN2A, are common in MM, suggesting that these markers can help differentiate malignant from reactive mesothelial cells, enhancing diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion. Hiroshima, K., Wu, D., Hamakawa, S., et al.[2021]

Malignant mesothelioma is a challenging cancer primarily caused by environmental factors like asbestos, and most patients are not suitable for surgery or radiation, leaving cytotoxic agents as the main treatment option.

Recent trials have shown that pemetrexed, when combined with cisplatin, can achieve a response rate of 14.1% and a 1-year survival rate of 47.8%, indicating potential efficacy in treating this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging insights into the biology and therapy of malignant mesothelioma. Vogelzang, NJ.[2022]

Malignant mesothelioma, while not typically immunogenic, shows immune recognition, and patients exhibit impaired immune responses, making it a valuable model for studying immune-related biomarkers.

Various innovative treatments, including gene therapies and targeted inhibitors like ZD1839 and STI-571, are being tested in clinical trials, suggesting that a combination of therapies may be necessary for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents. Nowak, AK., Lake, RA., Kindler, HL., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intrapleural infusion of activated macrophages and gamma-interferon in malignant pleural mesothelioma: a phase II study. [2019]

2. France pubmed.ncbi.nlm.nih.gov

[Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update]. [2008]

3. United States pubmed.ncbi.nlm.nih.gov

HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Emerging insights into the biology and therapy of malignant mesothelioma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents. [2019]